Chromatography Column Distribution System

ABSTRACT

A chromatography column distribution system includes a set of first bed support ribs extending radially from an inner, first radial position near the centre of the plate to an outer radial position nearer to the periphery of the plate and at least one set of intermediate bed support ribs starting at an intermediate radial position and extending to an outer radial position nearer to the periphery of the plate. Channels are formed between adjacent bed support ribs. The desired local effective channel height varies in accordance with a predetermined formula from the first radial position to the outer radial position. The transverse cross-sectional areas of the ribs or the channels are adapted such that the actual local effective channel height is within 15% of the desired local effective channel height over portions of the distribution system situated between the first radial position and the outer radial position. The length of the portions correspond to at least 80% of the distance between the first and outer radial position and the outer radial position.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/420,408, filed Apr. 8, 2009, which is a continuation of U.S. patentapplication Ser. No. 10/571,194 filed Mar. 8, 2006, now U.S. Pat. No.7,534,345, issued May 19, 2009, which is a filing under 35 U.S.C. §371and claims priority to international patent application numberPCT/EP2004/010599 filed Sep. 22, 2004, published on May 31, 2005, as WO2005/028064, which claims priority to patent application number0322144.7 filed in Great Britain on Sep. 23, 2003, the disclosures ofwhich are incorporated herein by reference in their entireties.

FIELD OF THE INVENTION

The present invention relates to a liquid distribution system forchromatography columns. More specifically, the invention relates to ascalable liquid distribution system for large-scale chromatographycolumns.

BACKGROUND OF THE INVENTION

In separation procedures, particularly in liquid chromatography, thefluid distribution system is critical to the overall performance, andbecomes more so as the cross-section of the chromatographic columnincreases.

Columns used in liquid chromatography typically comprise a body-formingstructure enclosing a porous media through which a carrier liquid flows,with separation taking place by material distribution between thecarrier liquid and solid phase of the porous media. Typically, theporous media is enclosed in the column as a packed bed, typically formedby consolidating a suspension of discrete particles. An alternative tothe packed bed is the so-called expanded or fluidised bed, whereeffective porosity and volume of the expanded bed depends on the fluidvelocity. The term ‘packing’ shall be used in the following to describethe porous solid phase in all types of chromatography. The efficiency ofthe chromatographic separation relies in both modes strongly on theliquid distribution and collection system at the fluid inlet and outletof the packing.

Ideally, the carrier liquid is uniformly introduced throughout thesurface at the top of the packing, flows through the packing at the samelinear velocity throughout the packing cross section, and is uniformlyremoved at the plane defined by the bottom of the packing.

Conventional distribution systems for use in liquid chromatography mustaddress a number of inherent problems that have deleterious effects onthe separation efficiency of the column. Among these problems isnon-uniform initial fluid distribution at the top of the packing as wellas non-uniform fluid collection at the outlet of the packing. Theproblem of non-uniform initial fluid distribution refers generally tothe problem of applying a sample volume simultaneously over thecross-sectional area of the packing. Without a simultaneous introductionof fluid in the plane defined by the top of the packing, it is virtuallyimpossible to achieve uniform flow distribution through the packing.

This will lead to increased dispersion in the chromatographic system bybroadening the convective residence time distribution of a tracersubstance transported with the fluid throughout the system. Thedispersion generated by the liquid distribution system has to becontrolled in relation to the amount of dispersion introduced by thechromatographic packing itself by means of diffusion and mixing effects.

Standard fluid distribution systems consist of one central inlet, formedin the end plate of the column, for the mobile phase in combination witha thin distribution channel (gap) behind the filter (woven net orsinter) or bed support at the inlet end of the column and a similarfluid collection system at the outlet end of the column. The filter orbed support is supported by ribs which extend from the inner surface ofthe end plate to side of the filter or bed support facing the end plate.The ribs extend radially and the spaces between the ribs formdistribution channels for distributing the fluid. Each rib has a taperedend section facing the centre of the column and a body of substantiallyconstant width extending from the tapered section to the wall of thecolumn. At given radial positions, the number of ribs doubles in orderto maintain the necessary mechanical support of the filter/bed support.In columns, the local effective cross-sectional area for fluid flow inthe distribution channels at a radial position r is defined by the depthof the channels h, the width of the channels w and the number ofchannels. The local effective channel height (i.e. the height at alocation at a given radial distance from the centre of the column) forfluid flow in a column is defined as the local height of a correspondingopen channel (i.e. a rib-free channel) having the same cross-sectionalarea for fluid flow as the total cross-sectional area of the channels inthe actual column at the same radial distance. Thus, if in a particularcolumn the channel height at a distance R from the column centre was 4mm and half of the cross-sectional area was occupied by ribs at distanceR, then the effective channel height at distance R would be 2 mm. It isconsidered desirable that the local effective channel height varieslinearly from the centre of the column to the column wall in order togive the desired fluid distribution over the filter or bed support.However, in the prior art, no account has made of the effect that thesize and number of ribs has on the local effective channel height. Thiscan be seen in FIG. 3 in which the solid line shows the calculatedeffective channel height (ECH) against radial distance (R) from thecentre of the column for a typical prior art column with ribs startingat R=55 mm and R=110 mm, while the dotted line shows the desired linearvariation in local effective channel height. At R=55 mm the actual localeffective channel height is 3.2 mm while the desired local effectivechannel height is 3.8 mm, i.e. only 84% of the desired value, and atR=112 mm the actual local effective channel height is 1.4 mm—only 56% ofthe desired height is 2.5 mm. Clearly, there is a local decrease in theeffective channel height, and therefore throttling of the flow in thedistribution channels, at the radial positions where the number of ribsdoubles. This causes a local pressure increase which has a negativeimpact on the chromatographic performance.

SUMMARY OF THE INVENTION

According to the present invention, at least some of the problems withthe prior art are solved by means of a device having the featurespresent in the characterising part of claim 1.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1a ) shows schematically a plan view of a prior art distributionplate for a chromatography column;

FIG. 1b ) shows a cross-section along line I-I in FIG. 1a );

FIG. 1c ) shows an enlarged view of a portion of the plan view of FIG.1a );

FIG. 1d ) shows a perspective view of the portion of the prior artdistribution plate shown in FIG. 1c );

FIG. 2a ) shows schematically a plan view of a first embodiment of achromatography column distribution plate in accordance with the presentinvention.

FIG. 2b ) shows an enlarged view of a portion of the plan view of FIG.2a );

FIG. 2c ) shows a perspective view of the portion of the prior artdistribution plate shown in FIG. 2b );

FIG. 3 is a graph showing effective channel height (ECH) against radialdistance (R) for a prior art column; and,

FIG. 4 is a graph showing effective channel height (ECH) against radialdistance (R) for an embodiment of a column in accordance with thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

FIGS. 1a )-1 d) show schematically views of a prior art distributionsystem. Distribution plate 1 comprises a body 3 in the form of a discwith a central inlet orifice 5. A plurality of first bed support ribs 7of length L1 extend radially from the region at a distance R1 from thecentre of the surrounding the orifice 5 to substantially the periphery 9of the body 3. Each first bed support rib 7 has a maximum height h1 atits first end 6 near to or at the orifice 5 and a minimum height h2 atits second end 8 near to or at the periphery 9 of the body 3. The heightof the each first bed support rib 7 varies linearly from the first end 6to the second end 8. Each first end 6 is tapered with a tapered portion10 of length t1 facing towards the central inlet orifice 5. Each firstrib has an elongated rib body 11 of length (Lt−t1) with a substantiallyconstant width w1 between the tapered portion 10 of each first end 6 andthe second end 8.

Starting at a first intermediate radial position R2 situated between theorifice 5 and the periphery 9, a plurality of second, intermediate, bedsupport ribs 17 of length L2 which is less than L1 are positionedbetween the first bed support ribs 7. Each second bed support rib 17 hasa tapered portion 16 of length t2 which faces towards the central inletorifice 5, and an elongated rib body 18 of length (L2−t2) with asubstantially constant width w1. These second bed support ribs 17 extendfrom first intermediate radial position R2 to substantially theperiphery 9 of the body 3.

Starting at a second intermediate radial position R3 situated betweenthe orifice 3 and the periphery 9 at a distance greater than R2 from theorifice 3, a plurality of third, intermediate, bed support ribs 19 oflength L3 are positioned between the first bed support ribs 7 and thesecond bed support ribs 17. Each third bed support rib 19 has a taperedportion 21 of length t3 which faces towards the central inlet orifice 5,and an elongated rib body 23 of length (L3−t3) with a substantiallyconstant width w1. These third bed support ribs 19 extend from secondintermediate radial position R3 to near to the periphery 9 of the body3.

Channels 13 are formed by the gaps between the ribs 7, 17, 19.

As can be understood from the FIGS. 1a )-1 d), at the regions in thevicinity of the radial positions R2 and R3 there is a reduction in thelocal cross-sectional area of the channels 13 due to the presence of thesecond, respectively, third support ribs. This reduction in the localcross-sectional area causes a local throttling of the flow though thechannels 13 which is manifested as a local pressure increase. Thisdisturbs the flow through the distribution system and has a negativeimpact on the performance of the chromatography column.

FIGS. 2a )-2 c) show schematically views of a first embodiment of adistribution plate 101 in accordance with the present invention.Distribution plate 101 comprises a body 103 in the form of a disc with acentral inlet orifice 105. A plurality of first bed support ribs 107 oflength LL1 extend radially from an inner, first radial position R1 nearto the orifice 105 to an outer radial position near to the periphery 109of the body 103. Each first bed support rib 107 has a maximum height atits first end 106 near to or at the orifice 105 and a minimum height atits second end 108 near to or at the periphery 109 of the body 103. Theheight of the each first bed support rib 107 varies linearly from thefirst end 106 to the second end 108. Each first end 106 is tapered witha tapered portion 110 of length t11 facing towards the central inletorifice 105. Each first rib 107 has an elongated rib body 111 of length(LL1−t11) which extends from the point of maximum width of the taperedportion 110 to the second end 108. As explained below, elongated rib 111body does not have a constant width along its length.

Starting at a first inner intermediate radial position R2 situatedbetween the orifice 105 and the periphery 109, a plurality of firstintermediate bed support ribs 117 of length LL2 (which is less than LL1)are positioned between the first bed support ribs 107. Each firstintermediate bed support rib 117 has a tapered portion 116 of length t12which has a pointed end that faces towards the central inlet orifice105, and an elongated rib body 118 of length (LL2−t12) with a varyingwidth as described below. These first intermediate bed support ribs 117extend from first intermediate radial position R2 to the outer radial 10position near to the periphery 109 of the body 103.

Starting at a second inner intermediate radial position R3 situatedbetween the orifice 105 and the periphery 109 at a distance greater thanR2 from the orifice 103, a plurality of second intermediate, bed supportribs 119 of length LL3 are positioned between the first 15 bed supportribs 7 and the first intermediate bed support ribs 117. Each second bedsupport rib 119 has a tapered portion 121 of length t13 which has apointed end that faces towards the central inlet orifice 105, and anelongated rib body 123 of length (LL3−t13) with a varying width. Thesesecond intermediate bed support ribs 119 extend from second innerintermediate radial position R2 to the outer radial position near to theperiphery 109 of the body 103.

Channels 113 are formed by the gaps between the ribs 107, 117, 119. Inthis embodiment the local effective channel height decreases in a morelinear manner than in prior art devices (i.e. the maximum differencebetween the desired local effective channel height and the actual localeffective channel height is less than 15.5% of the desired local channelheight) from the position R1 to the periphery of the column). This isachieved by the widths of the elongated rib bodies 111, 118 and 123being varied along their lengths in order to reduce or eliminatediscontinuities (that is, abrupt local changes) in the cross sectionalarea of the channels 113 formed between ribs. This may be achieved byadapting the width of the elongated body 111 of each first support rib107 at the position along its length where it is adjacent the taperedportion 116 of a first intermediate support rib 117 and/or secondintermediate support rib 119 and/or by adapting the width of theelongated body 118 of each first intermediate support rib 117 at theposition along its length where it is adjacent the tapered portion 121of a second intermediate support rib 119 so that the actual localeffective channel height is at worst within 15% of, preferably is within10% of, more preferably is within 5% of, and most preferably is the sameas the desired local effective channel height. In order to reducediscontinuities in the cross sectional area of a channel at the radialpositions where there are first and second intermediate support ribs117, 119, the width of each elongated body 111 at any radial position isthe adapted to partly or completely compensate for the reduction inchannel cross sectional area caused by the presence of the intermediatesupport rib 117 so that the actual local effective channel height is atworst within 15% of the desired local channel height. Preferably theactual local effective channel height is within 10% of, more preferablyit is within 5% of, and most preferably is the same as the desired localeffective channel height over most of the length of the longest ribs.This is achieved by adapting the tangential cross sectional area of eachelongated rib body 111 at a radial position Rx by an amount equal to, orslightly more than, or slightly less than, the tangential crosssectional area of an adjacent intermediate support rib 117 at the sameradial position Rx. In this embodiment of the present invention, inorder to keep the cross sectional area of a channel constant at theradial positions where there are first, first intermediate and secondintermediate support ribs, the reduction in channel cross sectional areacaused by the presence of a second intermediate support rib 119 iscompensated for by adapting the widths of both first and firstintermediate support ribs 107 and 117 equally at every radial positionRx by an amount equal to half of the reduction in channel crosssectional area caused by the presence of a second intermediate supportrib 117.

FIG. 4 is a graph showing the local effective channel height (ECH)against radial position (R) for a column distribution system inaccordance with the present invention in which the distribution systemhas two sets of ribs—the first set starting at R=55 mm and the secondset starting at R=110 mm. as can be seen in FIG. 4. In FIG. 4 themaximum deviation of the actual local effect column height (shown by asolid line) from the desired local effective column height (shown by adotted line) occurs at R=110 m where the actual effective channel heightis 1.6 mm and the desired effective channel height is 1.5 15 mm—adifference of only 6.7%. In this column, over the length of the longestribs, the lengths of the portions of the channels which have an actuallocal effective channel height that is within 5% of the desired localeffective channel height, when added together, correspond to more than80% of the length of longest of these ribs.

Preferably, distribution systems in accordance with the presentinvention are machined so that the portions of the distributions systemwhere the actual local effective channel height is within 5% of thedesired local effective channel height correspond to more than 90% ofthe length of the longest ribs. More preferably, distribution systems inaccordance with the present invention are machined so that the actuallocal effective channel height is within 5% of the desired localeffective channel height for more than 95% of the length of these ribs.Most preferably, distribution systems in accordance with the presentinvention are machined so that the actual local effective channel heightis within 5% of the desired local effective channel height for 100% ofthe length of these ribs.

In another embodiment of the present invention instead of compensatingfor the reduction of the channel width caused by the presence of a thirdsupport rib 119 by adapting the width of both elongated rib bodies 111and 118, the width of just one type of elongated rib body, e.g.elongated rib bodies 118 can be adapted.

In a further embodiment of the present invention, instead ofcompensating for the reduction of the channel width caused by thepresence of a second and further support ribs by adapting the width oflonger rib bodies, the height of the channel between the ribs can beadapted.

While the present invention has been illustrated by examples ofembodiments of distribution systems for columns in which the localeffective channel is intended to vary linearly in the radial direction(i.e. local effective column height is proportional to the inverse ofthe radial distance from the centre of the column), it is alsoconceivable to apply the present invention to distribution systems forcolumns where the local effective channel height is not intended to varylinearly but in a curve in accordance with another formula, for example,local effective column height is proportional o the inverse of thesquare of radial distance from the centre of the column.

By increasingly accurately adapting the dimensions of the ribs, it ispossible to achieve a distribution system in accordance with the presentinvention where the actual local effective channel height is within 5%of the desired channel height over the whole length of the ribs. Byusing highly accurate computer-controlled production methods it ispossible to produce a distribution system with an actual local effectivechannel height that is substantially the same as the desired localeffective channel height over the whole length of the ribs.

The above mentioned embodiments are intended to illustrate the presentinvention and are not intended to limit the scope of protection claimedby the following claims.

What is claimed is:
 1. A chromatography column distribution system (101)comprising a set of first bed support ribs (107) extending radially froman inner, first radial position (R1) near the centre of the plate to anouter radial position nearer to the periphery (109) of the plate and atleast one set of intermediate bed support ribs (117, 119) starting at anintermediate radial position (R2, R3) and extending to an outer radialposition nearer to the periphery (109) of the plate (101), wherebychannels are formed between adjacent bed support ribs (107, 117, 119)and the desired local effective channel height is intended to vary inaccordance with a predetermined formula from said first radial position(R1) to said outer radial position, wherein the transversecross-sectional areas of said ribs (107, 117, 119) or said channels areadapted such that the actual local effective channel height is within15% of the desired local effective channel height over portions of thedistribution system situated between said first radial position (R1) andsaid outer radial position, wherein the total length of said portionscorrespond to at least 80% of the distance between said first radialposition (R1) and said outer radial position.